The objective of this project is to identify and characterize molecules that regulate cell proliferation in normal and neoplastic cells and to understand the mechanism of action of these molecules. This proposal is based on the hypothesis that growth factors regulate cell proliferation and that one way in which neoplastic transformation allows cells to become cancerous is to alter cellular growth factor requirements. The response of normal and malignant cells in vitro to two mitogens, platelet-derived growth factor (PDGF) and epidermal growth factor (EGF) will be evaluated. The growth stimulatory effects of these molecules on normal and malignant human epithelial cells, SV40-transformed rodent cells and revertants of these transformed cells, will be investigated. Mutants temperature-sensitive in their response to mitogens will also be isolated and characterized. These latter experiments should help to define the cellular processes that occur in the process of growth stimulation by mitogens. The following specific projects will be undertaken: 1. Evaluate the response of normal and malignant human epithelial cells to platelet-derived growth factor (PDGF) and epidermal growth factor (EGF). 2. Determine if transformation by the oncogenic virus SV40 alters the cellular requirement for platelet-derived growth factor. This will be done by investigating the ability of temperature-sensitive mutants and deletion mutants of SV40 to induce DNA synthesis in cultures of rodent cells maintained in the absence of platelet-derived growth factor. 3. Determine if revertants of SV40-transformed cells have increased requirements for PDGF and EGF. 4. Measure the levels of various SV40-specific antigens within these revertant cells. This will be done by immunoprecipitation with specific antisera. 5. Isolate mutants of 3T3 cells temperature sensitive in their response to PDGF and EGF.